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The huge impact of kinetic energy released by the breaking of hard roof is one of the important factors that induces dynamic disasters in coal mines. The key to preventing and controlling coal and rock dynamic disasters is the directional fracture of strata at a specific position and reducing the length of hard roof suspension. The multi-hole sleeve fracturing technology has the advantages of simple operation and wide application conditions and has a wide research prospect in the field of hard roof weakening. In order to understand the mechanism of multi-hole sleeve fracturing, the mechanical mechanism of multi-hole sleeve fracturing was studied using theoretical analysis and numerical simulation. The variation law of inter-hole stress under different influencing factors was revealed, and the crack propagation law and force chain distribution characteristics in the fracturing process were obtained. The pre-cracking effect of sleeve fracturing can be improved by changing the drilling structure through grooving. In order to determine the reasonable hole arrangement parameters, a mechanical model of the multi-hole sleeve fracturing with prefabricated cracks was established based on linear elastic fracture mechanics. The calculation equations of stress intensity factor, critical expansion pressure, and critical crack initiation angle of cracks were given, and the variation rules of stress intensity factor, critical expansion pressure, and critical crack initiation angle of cracks under different influencing factors were obtained. The results show that: ① The lateral pressure coefficient k has a significant effect on the minimum crack initiation stress of the borehole. With the lateral pressure coefficient k > 1, the minimum crack initiation stress decreases with the increase of the hole angle. With the lateral pressure coefficient k < 1, the minimum crack initiation stress decreases with the increase of the hole angle. ② The numerical simulation results show that there is a stress superposition effect between the sleeves, and the contact force chain is a 'radial' distribution. The fracturing process of the sleeve is mainly a tensile failure, and the deformation and failure at the connection of the hole center is the most severe, forming a 'banded' fracture surface along the direction of the hole. ③ The stress distribution near the slot end is changed by the slot, and the circumferential tensile stress is larger than that of the seamless slot model. When the slot length is 0.5 times the radius of the hole, the critical expansion pressure is the smallest, and the crack is most likely to expand. ④ The critical initiation angle is determined by KI and KII, which is less than 70.53°. Under the condition that the pump pressure and in-situ stress conditions cannot be changed, the directional fracturing of the rock can be realized by adjusting the hole angle and the length of the prefabricated slot.

In order to reveal the micromechanics of rock failure mechanisms and energy transfer patterns under different confining pressures during sleeve fracturing, a PFC3D numerical model was established based on sleeve fracturing tests and expansive force measurement experiments. The discrete element method was employed for the numerical simulation of the sleeve fracturing process. In addition, by integrating acoustic emission data, the influence of varying confining pressures on the development of microcracks in rocks and the corresponding energy variations were explored. Furthermore, the mechanical mechanism for sleeve fracturing was revealed based on the principles of elasticity. The results show that : ① There is a pressure loss in the process of sleeve liquid injection. According to the pressure loss rate, the liquid injection process can be divided into three stages: filling, pressurization, and rapid pressurization. The expansion force of the sleeve exhibits a linear relationship with the injection pressure, with a correction coefficient of 0.678. ② The PFC3D numerical model effectively represents the mechanical properties and deformation failure characteristics of rocks during sleeve fracturing, where tensile failure is the predominant mode of rock fracturing. The propagation path of cracks is determined by the confining pressure, which also suppresses the generation of microcracks within the rock. As the differential stress increases, both the number and proportion of shear cracks inside the rock gradually increase. ③ Acoustic emission signals can be divided into quiescent and active periods, with the cumulative number of cracks showing a stepwise increase. The characteristics of acoustic emission exhibit a single-peak distribution under unconfined conditions and a multi-peak distribution under confined conditions, indicating the presence of multiple fracture stages. ④ The influence scope of the sleeve expansion force is limited, and the sleeve expansion force exhibits a logarithmic correlation with the circumferential tensile stress. The tangential stress increases with the increase of stress difference. When the angle φ is 45° or 135°, the shear damage inside the rock is most obvious. ⑤ The energy input into the rock decreases as the confining pressure increases under the same expansive force. Under different confining pressures, the input energy, elastic energy, and dissipation energy of rock increase sharply in different degrees, which is mainly due to the expansion of the borehole caused by the formation of macro cracks. The growth rate of dissipative energy is faster than the elastic energy, approximately 1.27 to 1.55 times that of the elastic energy.

Abstract It is urgent to develop low-reflection electromagnetic interference shielding material to shield electromagnetic waves (EMW) and reduce their secondary radiation pollution. Herein, an electromagnetic interference shielding nanofiber film is composed of ZnO and carbon nanofiber (CNF) via electrospinning and carbonization approachs, and subsequently coating perfuorooctyltriethoxysilane as a protective layer. On the one hand, ZnO coated by porous carbon, which is derived from ZIF-8, endows the nanofiber film low reflection property through optimizing impedance matching between free space and the nanofiber film. On the other hand, the nanofiber film possesses high electromagnetic interference shielding efficiency, which is beneficial by excellent electrical conductivity of CNF derived from waste leather scraps. Furthermore, the nanofiber film involves abundant interface, which contributes to high interfacial polarization loss. Thus, the nanofiber film with a thickness of 250 μm has electrical conductivity of 53 S/m and shielding efficiency of 50 dB. The reflection coefficient of the nanofiber film is inferior to 0.4 indicates that most of EMW are absorbed inside the materials and the nanofiber film is effective in reducing secondary radiation contamination of electromagnetic waves. Fortunately, the nanofiber film exhibits outstanding solar harvesting performance (106 ℃ at 1 sun density) and good self-cleaning performance, which ensure that the nanofiber film can work in harsh environments. This work supplies a credible reference for fabricating low-reflection electromagnetic shielding nanofiber film to reduce secondary radiation pollution and facilitates the upcycling of waste leather scraps. Graphic abstract

ABSTRACT: Sperm motility is an important index for the evaluation of semen quality. Improving sperm motility is important to improve reproductive performance, promote breeding process, and reduce production cost. However, the molecular mechanisms regulating sperm motility in chickens remain unclear. In this study, histological observation and whole-transcriptome analysis were performed on testicular tissue of chickens with high and low sperm motility. Histological observations showed that roosters with high sperm motility exhibited better semen quality than those with low sperm motility. In addition, the germinal epithelial cells of roosters with low sperm motility were loosely arranged and contained many vacuoles. RNA-seq results revealed the expression of 23,033 mRNAs, 2,893 lncRNAs, and 515 miRNAs in chicken testes. Among them, there were 417 differentially expressed mRNAs (DEmRNAs), 106 differentially expressed lncRNAs (DElncRNAs), and 15 differentially expressed miRNAs (DEmiRNAs) between high and low sperm motility testes. These differentially expressed genes were involved in the G protein-coupled receptor signaling pathway, cilia structure, Wnt signaling, MAPK signaling, GnRH signaling, and mTOR signaling. By integrating the competitive relationships between DEmRNAs, DElncRNAs, and DEmiRNAs, we identified the regulatory pathway of MSTRG.3077.3/MSTRG.9085.1-gga-miR-138-5p-CADM1 and MSTRG.2290.1-gga-miR-142-3p-GNAQ/PPP3CA as crucial in the modulation of chicken sperm motility. This study provides new insights into the function and mechanism of ceRNAs in regulating sperm motility in chicken testes.

ABSTRACT: Intramuscular fat (IMF) is an important factor affecting chicken quality. However, the age-related mechanism of IMF deposition has not yet been elucidated. In this study, the IMF, phospholipids (PL), triglycerides (TG), and fatty acid (FA) content in the breast muscle of Beijing-You chicken (BJY) at 1, 56, 98, and 120 d of age was measured, and mRNA and miRNA sequencing was integrated to explore the regulatory genes of IMF deposition. The results showed that the IMF content of BJY at 1 d of age was significantly higher than that at later stage of birth (P < 0.05). The transcriptome sequencing results showed that 7, 225 differentially expressed genes (DEGs) and 243 differentially expressed miRNAs (DE-miRNAs) were identified. The cluster analysis showed that the expression of DEGs and DE-miRNAs at 1 d of age was significantly different from that at later stages of birth. Furthermore, a potential mRNA-miRNA regulatory network related to IMF deposition was established by weighted gene co-expression network analysis (WGCNA); gga-miR-29c-3p-PIK3R1, gga-miR-6701-3p-PTEN, gga-miR-363-3p-PTEN, gga-miR-1563-WWP1, gga-miR-449c/d-5p-TRAF6, and gga-miR-6701-3p-BMPR1B were identified as key mRNA-miRNA pairs for the regulation of IMF deposition. These results will help elucidate the mechanism of IMF formation mediated by miRNAs in chickens, and provide a theoretical foundation for the genetic improvement of broiler meat quality.

Introduction: Lipopolysaccharide (LPS) causes lesions of the epithelial barrier, which allows translocation of pathogens from the intestinal lumen to the host’s circulation. Hydrogen sulfide (H2S) regulates multiple physiological and pathological processes in colonic epithelial tissue, and CBS-H2S axis involved in multiple gastrointestinal disorder. However, the mechanism underlying the effect of the CBS-H2S axis on the intestinal and systemic inflammation in colitis remains to be illustrated. Objectives: To investigate the effect of CBS-H2S axis on the intestinal and systematic inflammation related injuries in LPS induced colitis and the underlying mechanisms. Methods: Wild type and CBS−/+ mice were used to evaluate the effect of endogenous and exogenous H2S on LPS-induced colitis in vivo. Cytokine quantitative antibody array, western blot and real-time PCR were applied to detect the key cytokines in the mechanism of action. Biotin switch of S-sulfhydration, CRISPR/Cas9 mediated knockout, immunofluorescence and ActD chase assay were used in the in vitro experiment to further clarify the molecular mechanisms. Results: H2S significantly alleviated the symptoms of LPS-induced colitis in vivo and attenuated the increase of COX-2 expression. The sulfhydrated HuR increased when CBS express normally or GYY4137 was administered. While after knocking kown CBS, the expression of COX-2 in mice colon increased significantly, and the sulfhydration level of HuR decreased. The results in vitro illustrated that HuR can increase the stability of COX-2 mRNA, and the decrease of COX-2 were due to increased sulfhydration of HuR rather than the reduction of total HuR levels. Conclusion: These results indicated that CBS-H2S axis played an important role in protecting intestinal barrier function in colitis. CBS-H2S axis increases the sulfhydration level of HuR, by which reduces the binding of HuR with COX-2 mRNA and inhibited the expression of COX-2.

Ni–Cu under-bump metallisation (UBM) can reduce stress and improve wetting ability in technology for electronic packaging technology advances with three-dimensional integrated circuit (3D IC) devices. The bond between the Sn-based solder and Ni–Cu UBM is affected by the formation of intermetallic compounds (IMCs), specifically Ni3Sn4 and (Ni,Cu)3Sn4. This paper investigates the mechanical properties of IMCs, which are critical in assessing the longevity of solder joints. First-principles calculations were carried out to investigate the phase stability, mechanical properties and electronic structures of Ni3Sn4, Ni2.5Cu0.5Sn4, Ni2.0Cu1.0Sn4, and Ni1.5Cu1.5Sn4 IMCs. The calculated formation enthalpies show that the doping of Cu atoms leads to a decrease in the stability of the phases and a reduction in the mechanical properties of the Ni3Sn4 crystal structure. As the concentration of Cu atoms in the Ni3Sn4 cells increases, the bulk modulus values of (Ni,Cu)3Sn4 formed with different compositions decrease from 107.78 GPa to 87.84 GPa, the shear modulus decreases from 56.64 GPa to 45.08 GPa, and the elastic modulus decreases from 144.59 GPa to 115.48 GPa, indicating that the doping of Cu atoms into the Ni3Sn4 cells may adversely affect their mechanical properties and increase the possibility of microcracking at the interface during actual service. The anisotropy of (Ni,Cu)3Sn4 is more significant than that of Ni3Sn4, with Ni2.0Cu1.0Sn4 showing the highest anisotropy. After evaluating the electronic structures, the metallic properties of Ni3Sn4 and the Ni2.5Cu0.5Sn4, Ni2.0Cu1.0Sn4, and Ni1.5Cu1.5Sn4 phases are revealed by electronic structure analysis. The total density of states (TDOS) for (Ni,Cu)3Sn4 structures is mainly influenced by Ni-d and Cu-d states. The addition of Cu atoms can increase the brittleness of Ni3Sn4. In addition, the region where d and p hybridisation occurs gradually increases with increasing Cu content. The electronic properties suggest that the binding energy between Ni and Sn atoms weakens with the addition of Cu atoms, resulting in a decrease in the elastic modulus. This research can serve as a valuable reference and theoretical guide for future applications of these materials.

To address the support difficulties caused by the dynamic pressure from the adjacent working face in gob-side entry driving, this study, taking the 8103 working face of the Jinhuagong Coal Mine in Shanxi Province as an example, adopted methods such as theoretical analysis, physical experiments, numerical simulations, and field practices to explore roof-cutting and pressure-relieving techniques to control the surrounding rocks in gob-side entry driving with small coal pillars under dynamic pressure. Fractures of the lateral roof, stresses on the surrounding rock, and deformations with different cutting-roof parameters were analyzed to determine the reasonable parameters for applications. The following results have been obtained. The longer the lateral cantilever length of the roof, the greater the load borne by the surrounding rock. Therefore, the key to reducing the confining pressure in a roadway is reducing the lateral cantilever length of the roof. After roof cutting, the roof of the gob area collapsed more completely. The stress on both sides of the coal pillar and that on the ribs of the solid coal dropped by 7.72 MPa and 4.16 MPa, respectively. The key roof-cutting parameters were analyzed by the UDEC numerical software, and the reasonable roof-cutting angle and height were determined to be 12° and 14 m. A support scheme combining “steel strip + bolt + anchor cable + roof cutting” was proposed. With the scheme applied, the displacement of both sides of the coal pillar was 61 mm shorter than that in the non-test section, and the duration in which the roadway was affected by mining was 11 days shorter. Therefore, the rationality of the selected roof-cutting and support parameters in this study is verified. The proposed scheme can effectively control the stability of surrounding rocks in gob-side entry driving with small coal pillars under dynamic pressure.

Abstract Identifying the mechanism of glioma progression is critical for diagnosis and treatment. Although studies have shown that guanylate-binding protein 2(GBP2) has critical roles in various cancers, its function in glioma is unclear. In this work, we demonstrate that GBP2 has high expression levels in glioma tissues. In glioma cells, depletion of GBP2 impairs proliferation and migration, whereas overexpression of GBP2 enhances proliferation and migration. Regarding the mechanism, we clarify that epidermal growth factor receptor (EGFR) signaling is regulated by GBP2, and also demonstrate that GBP2 interacts directly with kinesin family member 22(KIF22) and regulates glioma progression through KIF22/EGFR signaling in vitro and in vivo. Therefore, our study provides new insight into glioma progression and paves the way for advances in glioma treatment.

Abstract Background The role of hydrogen sulfide (H2S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H2S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H2S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. Methods Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H2S was detected by H2S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. Results Overexpression of CBS and exogenous H2S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H2S axis on colon cancer cells. Conclusions Overexpression of CBS and exogenous provision of H2S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.

Coal fly ash (CFA), an industrial solid waste, has been predominantly used a substitute for material in the concrete industry. Its reactivity is usually a crucial factor for use in cementitious composites. Conventionally physical and chemical treatments have been used to modify CFA for improving reactivity, but there still are some limitations such as easy agglomeration of particles, high cost, high energy-consumption, environmental pollution, etc. Herein, a feasible bio-modification treatment on CFA using Paenibacillus mucilaginosus is proposed. Adhesion and desilication of the bacteria & metabolites change the morphology, size distribution and surface properties of CFA. Compared with CFA, the bio-modified CFA (BCFA) has coarser surface, finer particle size, larger specific surface area (SSA), higher surface calcium content and lower surface Si/Al ratio. The characteristic changes contribute to enhancing the reactivity of BCFA relating to morphological, pozzolanic, micro-aggregate and interfacial effects in cementitious composites. The strength activity index (SAI) of BCFA reaches 90.8% at 28 d and increases 27.7% compared to that of CFA. Soluble silicon content in the bioleaching system shows significantly positive correlations with the SSA and SAI of BCFA (P

Increased xCT and transsulfuration pathway has been associated with metabolic reprogramming of colorectal cancer. However, the correlation between these 2 events and the underlying molecular mechanism remains obscure. xCT expression was determined in tissue microarrays of colorectal cancer. RNA sequencing and functional assays in vitro was adopted to delineate the involvement of transsulfuration pathway in the proper function of xCT in maintaining the chemoresistant phenotype. The synthetic lethality of blocking xCT and the transsulfuration pathway was investigated both in vitro and in vivo. The up-regulation of the transsulfuration pathway after inhibiting xCT in colon cancer cells was evident and exogenous H2S partially reversed the loss of chemoresistance phenotype after inhibiting xCT. Mechanistically, CTH derived H2S increased the stability of xCT through persulfidation of OTU domain-containing ubiquitin aldehyde-binding protein 1 at cysteine 91. AOAA and Erastin resulted in synthetic lethality both in vitro and in vivo, which was mediated through increased ferroptosis and apoptosis. Our findings suggest that a reciprocal regulation exists between xCT and the transsulfuration pathway, which is a targetable metabolic vulnerability. Mechanistically, CTH derived H2S increased the stability of xCT through persulfidation of OTU domain-containing ubiquitin aldehyde-binding protein 1 at cysteine 91.

Decoding arbitrary polarization information from an optical field has triggered unprecedented endeavors in polarization imaging, remote sensing, and information processing. Therefore, developing a polarization detection device with full on‐chip integration and miniaturization holds tremendous potential for many areas of optical sciences. Herein, a full‐Stokes polarimetry device for visible light based on an all‐dielectric metasurface is proposed. By combining both geometric phase and propagation phase modulation, the metasurface to provide two uncorrelated phase profiles for the two orthogonal states of input polarization is designed, which is then used to spatially separate the various polarization states of incident light. Through the use of a millimeter‐scale multiplexed metasurface array, successful characterization of the full polarization distribution of space‐variant polarization fields is further achieved. This proof‐of‐concept ultracompact and ultrathin metasurface is expected to open new pathways in full‐Stokes polarization detection, machine vision, and navigation.

The tailwater tunnel of the Wuyue pumped storage power station is located in bedrock and extends to depths between tens and hundreds of meters. It is impossible to analyze and evaluate the whole engineering area from geological exploration data, and the hydrogeological conditions are complicated. In the early stages of the tailwater tunnel’s construction, the drinking water wells in four villages dried up. This paper reports the results from a field investigation, in situ tests, laboratory tests, and numerical simulation carried out to determine how the groundwater was affected when the tunnel was excavated. A hydrogeological model of the region was established from the inverted regional natural flow field parameters. The model was validated, and an analysis of the errors showed that there was an average error of 1.98% between the natural flow field and the hydrogeological survey flow field. The model was then used to simulate the three-dimensional transient seepage fields under normal seepage conditions and limited seepage conditions, as far as was practical. The results showed that, as the excavation of the tailwater tunnel advanced, the water inflow to the tunnel also increased. When the water inflow increased from 1000 to 5000 m3/d, the water level at a distance of 100 m from the axis of the tunnel dropped from −0.956 to −1.604 m. We then analyzed how the water level changed as the water inflow varied and proposed a formula for calculating the extent of the influence on the groundwater. We studied how the water level changed at different well points to ascertain how a groundwater well became depleted and determined the factors that influenced seepage in the regional flow field. The water level in different areas of the project area was simulated and analyzed, and the extent of the groundwater area affected by the tunnel construction was clarified. We then studied how the groundwater in different areas of, and distances from, the project area was influenced by normal seepage conditions and limited seepage conditions and proposed a formula for calculating the extent of the influence on groundwater for different water inflows. We constructed a ‘smart site’ for visualizing data, sharing information, and managing the project. Time–frequency domain analysis was applied to explore the extent of the impacts and range of the vibration effects on residential housing at different distances from the project area caused by the different methods for excavating the tailwater tunnel. The results from this analysis will provide useful insights into how the excavation of this tailwater tunnel will impact the local residents and living areas.

The flavor of chicken meat is influenced by muscle metabolites and regulatory genes and varies with age. In this study, the metabolomic and transcriptomic data of breast muscle at four developmental stages (days 1, 56, 98, and 120) of Beijing-You chickens (BJYs) were integrated and 310 significantly changed metabolites (SCMs) and 7,225 differentially expressed genes (DEGs) were identified. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SCMs and DEGs were enriched in amino acid, lipid, and inosine monophosphate (IMP) metabolism pathways. Furthermore, genes highly associated with flavor amino acids, lipids, and IMP were identified by a weighted gene co-expression network analysis (WGCNA), including cystathionine β-synthase (CBS), glycine amidinotransferase (GATM), glutamate decarboxylase 2 (GAD2), patatin-like phospholipasedomain containing 6 (PNPLA6), low-specificity L-threonine aldolase (ItaE), and adenylate monophosphate deaminase 1 (AMPD1) genes. A regulatory network related to the accumulation of key flavor components was constructed. In conclusion, this study provides new perspectives regarding the regulatory mechanisms of flavor metabolites in chicken meat during development.

This paper aimed at constructing a systematic framework and examining the effect of gamification in programming education through a meta-analysis conducted on 21 empirical studies published in the last decade. We examined the effects of game types, gamification applications, pedagogical agents, programming types, and schooling levels on students' academic achievement, cognitive load, motivation, and thinking skills in programming education by cross-tabulation analysis. Results verified the positive impact of gamification in programming education. Gamification has the largest effect on students' motivation, followed by academic achievement, whereas it has the least effect on students' cognitive load. As for game types, the reasoning strategy game is most effective on academic achievement, while the puzzle game is most effective on motivation. As for gamification application, the games as a competitive mechanism has the greatest impact on students’ thinking skills and motivation. However, when games were adopted as teaching tools or student works, the effects are mainly represented in academic achievement. Pedagogical agents have a limited effect on programming education. With regard to programming types, the effect of gamification is more pronounced in text-based programming rather than graphical programming. This study provided an analytic framework and shed light on potential directions for further studies in the field.

BackgroundGlobally, stomach adenocarcinoma (STAD)’s high morbidity and mortality should arouse our urgent attention. How long can STAD patients survive after surgery and whether novel immunotherapy is effective are questions that our clinicians cannot escape.MethodsVarious R packages, GSEA software, Metascape, STRING, Cytoscape, Venn diagram, TIMER2.0 website, TCGA, and GEO databases were used in our study.ResultsIn the TCGA and GEO, macrophage abundance of STAD tissues was significantly higher than that of adjacent tissues and was an independent prognostic factor, significantly related to the overall survival (OS) of STAD patients. Between the high- and low- macrophage abundance, we conducted differential expression, univariate and multivariate Cox analysis, and obtained 12 candidate genes, and finally constructed a 3-gene signature. Both low macrophage abundance group and group D had higher TMB and PD-L1 expression. Furthermore, top 5 common gene-mutated STAD tissues had lower macrophage abundance. Macrophage abundance and 3 key genes expression were also lower in the Epstein-Barr Virus (EBV) and HM-indel STAD subtypes and significantly correlated with the tumor microenvironment score. The functional enrichment and ssGSEA revealed 2 signatures were similar and closely related to BOQUEST_STEM_CELL_UP, including genes up-regulated in proliferative stromal stem cells. Hsa-miR-335-5p simultaneously regulated 3 key genes and significantly related to the expression of PD-L1, CD8A and PDCD1.Conclusionmacrophage abundance and 3-gene signature could simultaneously predict the OS and immunotherapy efficacy, and both 2 signatures had remarkable similarities. Hsa-miR-335-5p and BOQUEST_STEM_CELL_UP might be novel immunotherapy targets.

Abstract Background Cancer-associated fibroblasts (CAFs) play important roles in tumor progression. However, the behaviors of activated CAFs in gastric cancer remain to be determined. The aim of the present study was to investigate the correlations between activated gastric CAFs and the prognosis of patients with gastric cancer, and to determine the effects of activated CAFs on the malignant phenotype and 5-fluorouracil resistance in this cancer. Methods Ninety-five patients with primary gastric cancer were enrolled in this study. Activation states of gastric CAFs were evaluated by immunohistochemistry. A modified method for the primary culture of gastric CAFs was employed. Types of CAFs and activation states were identified by immunocytochemical and immunofluorescent staining. Cell co-culture and gastric CAF conditioned medium transfer models were established to investigate the paracrine effects of activated CAFs on the migration and invasion of gastric cell lines. The half maximal inhibitory concentration of 5-fluorouracil and levels of cell apoptosis were examined using cell viability assay and flow cytometry, respectively. Protein expression levels of associated molecules were measured by Western blotting. Results Kaplan–Meier survival curves showed that activated gastric CAFs identified via fibroblast activation protein were significantly related to poorer cumulative survival in gastric cancer patients. Five strains of CAFs were successfully cultured via the modified culture method, and three gastric CAFs strains were identified as activated gastric CAFs. The migration and invasion abilities of gastric cells were significantly enhanced in both the co-culture group and the conditioned medium group. The half maximal inhibitory concentration for 5-fluorouracil in BGC-823 cells was elevated after treatment with conditioned medium, and early apoptosis was inhibited. Additionally, an obvious elevation of epithelial–mesenchymal transition level was observed in the conditioned medium group. Conclusions Activated gastric CAFs correlate with a poor prognosis of cancer patients and may contribute to the malignant phenotype and the development of resistance to 5-fluorouracil via paracrine action in gastric cancer. Gastric CAFs with a specific activation state might be used as a tumor biomarker within the microenvironment for prognosis and as a new therapeutic target for chemoresistant gastric cancer.

Escherichia coli Nissle 1917 (EcN), a kind of probiotic, has been reported to have a protective effect on the intestinal barrier function and can ameliorate certain gastrointestinal disorders. In this study, the potential protective effect of EcN on the intestinal barrier function in a septic mouse model induced by cecal ligation and puncture (CLP) operation was investigated. FITC-Dextran 4,000 Da (FD-4) flux and the expression levels of tight junction (TJ) proteins were measured to evaluate the protective effect of EcN on the intestinal barrier function. Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcNsup) on the barrier dysfunction induced by TNF-α and IFN-γ in vitro; the plasma level of both the cytokines increased significantly during sepsis. Transepithelial electrical resistance (TEER) and FD-4 transmembrane flux were measured, and the localization of ZO-1 and Occludin was investigated by immunofluorescence. The expression of MLCK and the phosphorylation of MLC were detected by western blot. The activation of NF-κB was explored by immunofluorescence, and CHIP assays were performed to investigate the conjunction of NF-κB with the promoter of MLCK. The results indicated that EcN protected the intestinal barrier function in sepsis by ameliorating the altered expression and localization of TJ proteins and inhibiting the NF-κB-mediated activation of the MLCK-P-MLC signaling pathway which might be one of the mechanisms underlying the effect of EcN.

Individual recognition of fish within aquaculture fish groups is crucial for monitoring the growth status of each fish and is a key technology for precision and green aquaculture. However, accurately recognizing fish faces challenges due to the significant variations in fish postures and the influence of complex environments. This article aims to present a highly accurate method for underwater fish individual recognition, offering technical support for intelligent fish farming. To achieve this goal, a novel lightweight underwater fish individual recognition method based on local feature guidance training was proposed for precision aquaculture in this study. The method designs a multi-scale network based on deep learning and utilizes SE_ResNext for feature extraction. This network consists of a branch representing the global feature and a branch representing the local feature. During training, the full image of the fish individual is inputted as a coarse scale to the global branch (G-branch) to learn the global feature and calculate the ID loss. The image of each part formed after segmenting the fish individual is inputted as a fine-scale input to the partial branch (P-branch) to learn the local feature. Subsequently, the global feature and local feature are combined to form the fusion feature, and the Triplet loss and ID loss are calculated on the fusion feature. Finally, the loss calculated in the global feature and the loss calculated in the fusion feature are weighted and summed to obtain the total loss. Through the design of the loss function, the global feature is consistently influenced by the local feature, and the local feature serves to guide the global feature. During prediction, the global feature, having learned the information from the local feature, allows for the sole utilization of the G-branch to recognize fish individuals. This approach significantly reduces the number of parameters and computational requirements, resulting in a lightweight network. The method achieves high accuracy, with both Rank-1 and Rank-5 accuracy rates surpassing 95%. Remarkably, even with low image resolution and slight obscuration of the fish body, the Rank-1 accuracy remains above 90%. [ABSTRACT FROM AUTHOR]